Haemophilus influenzae b (Hib) and Streptococcus pneumoniae types 6, 12, and 14 cause much morbidity in infancy. Modest titers of antibody to their capsular polysaccharide (CP) antigens would be protective, but the present purified CP vaccines are not immunogenic in infancy. Means of enhancing the immunogenicity will be sought. Because animal models of immunogenicity are unsatisfactory, approaches are proposed that should also be safe in human experiments. The following modified antigens will be made and evaluated: (a) CP covalently coupled to a carrier protein appropriate for human use. The protein is CRM-197, a non-toxic "mutant" of diphtheria toxin, which is being developed as a diphtheria toxoid per se. Coupling will be direct--not via potentially toxic linker molecules. (b) oligosaccharides (of the CP) in a range of lengths coupled in varying ratios to CRM-197. (c) CP selectively oxidized at primary methoxy carbons to convert varying, defined proportions into carboxylate residues. (d) oligosaccharides as in (b) coupled to the CP of S. pneumoniae type 3 (the most speculative of the modifications). As a control the same modifications will be carried out also upon two CP that ordinarily are immunogenic in infants. Thus determinants from "infant-inactive" and "active" CP will be compared in the same molecular environments.